Biology of P5-type cation-transporting ATPases

在中枢神经系统的发育过程中，神经元的活动驱动突触连接的规范和成熟。神经元的成熟和功能接触的形成过程受到钙依赖基因表达的严格控制。钙在神经元功能包括成熟、分化和死亡中起着核心作用。我最近分离了五种新的蛋白质，称为ATP13A1到ATP13A5，被归类为钙转运蛋白。它们是膜离子转运蛋白P5型亚家族的成员。伴随发现号研究计划的主要焦点是了解这些转运蛋白在发育和成熟的神经系统中的生物学作用。我的主要目标是提供实验证据，证明人类P5转运蛋白参与钙稳态，并且它们具有不同于已知的主要钙泵的功能。为了实现我的研究计划中设定的目标，我将需要一个计算机控制的MasterCycle实时聚合酶链式反应系统，用于量化测量发育中大脑中的基因表达。我的实验室将是第一个研究人类亚家族P5型转运蛋白分子机制的实验室。实时聚合酶链式反应系统将立即用于启动我附带的Discovery应用程序中描述的实验。我目前提出的研究将对膜离子转运的性质提供新的见解，并将有助于阐明神经系统中钙调节的新的和独特的机制。

During the development of the central nervous system, neuronal activity drives the specification and maturation of synaptic connections. The process of neuronal maturation and formation of functional contacts is tightly controlled by calcium-dependent gene expression. Calcium plays a central role in neuronal function including maturation, differentiation, and death. I have recently isolated five novel proteins, called ATP13A1 to ATP13A5, classified as calcium transporters. They are members of the P5-type subfamily of membrane ion transporters. The main focus of the accompanying Discovery research program is to understand the biological role of these transporters in the developing and mature nervous system. My main objective is to provide experimental evidence that the human P5 transporters are involved in calcium homeostasis and that they have distinct functions from the major known calcium pumps. To achieve the goals set in my research program I will require a computer-controlled Mastercycler real-time PCR system for quantified measurement of gene expression in the developing brain. My laboratory will be the first to study molecular mechanisms of the human subfamily of P5-type transporters. The real-time PCR system will be used right away for initiating the experiments described in my accompanying Discovery application. My currently proposed research will provide new insights into the nature of membrane ion translocation, and it will help to elucidate novel and distinctive mechanisms of calcium regulation in the nervous system.